Those in COMB were significantly more likely to respond (QIDS-SR decrease ≥50% from baseline) at week 24 (end of treatment), compared with those in TAU (85% vs. 20%, P < 0.001), and the pattern was maintained at week 48 (88% vs. 33%, P < 0.001) (Table 4).
Those in COMB, compared to those in TAU were significantly more likely to be in remission (QIDS-SR <5) over the course of the study, P < 0.001 (Table 4). Week-specific rate differences were not calculated due to the few TAU cases in remission, but the pattern was evident from week 24 (65% vs. 10%) to week 48 (71% vs. 7%).
The COMB group, relative to TAU reported significantly less hopelessness (BHS) at all visits after baseline (Table 4). There was no change in life satisfaction reports over the course of the study. Similarly, CD4 counts and ARV adherence [approximately 80% at all visits (data not shown)] did not differ between groups during the study. HIV log10 VL decreased for the entire sample (main effect for time at weeks 36 and 38, P < 0.01), but groups did not differ in the rate of change. A post hoc analysis of variance, accounting for baseline VL, found an association between reduction in QIDS-SR scores and the final log10 VLs (F = 4.37, P < 0.05) among the entire sample.
Participants in COMB were more likely to receive psychotherapy than in TAU (95% vs. 45%, χ2 = 12.44, P < 0.001) and attended more sessions over the 24 weeks treatment period [12.6 (SD = 3.1) vs. 5.0 (SD = 2.2), t = 9.01, P < 0.001]. There was no difference in the rate of antidepressant use between the COMB and TAU groups over the course of the study (Table 4), and the complex details of medication usage in each condition will be reported subsequently. No significant adverse effects attributable to treatment medications were reported in either group.
Remission rates in this study are somewhat higher (71%) than reported in other clinical trials of combined CBT and medication management with nonmedically ill youth, where remission rates were between 37% and 45% at week 24.17,45–47 Several factors could account for the excellent rates observed in this study. Collaboration between the mental health therapist and medication prescriber has been shown to be a particularly effective approach in treating depression among adolescents in medical treatment settings, and the COMB treatment may have prompted increased collaboration.18 Also, the CBT and MMA were tailored for the unique issues of those YLWH, perhaps increasing the appeal, engagement, and efficacy of the treatments over and above TAU.
Reduction in VL were observed over time but was unrelated to treatment condition. Rather, reduced VL was significantly associated with reduced depression in the entire sample, confirming the general relationship between improvement in depression and better health. The lack of COMB impact on health indices could be due to the relatively small sample and associated lack of statistical power. Furthermore, participants were receiving care in HIV-specialty clinics whereby many participants were taking antiretroviral medications at baseline with relatively good adherence reported at the outset; as a result, there may have been less room for improvement.
Despite the strengths of this study, there are a number of limitations. The sample was recruited from HIV clinical care sites and youth with substance abuse disorders were excluded, so results may not be generalizable to all YLWH. Also, the results may not be generalizable to sites out of the United States or those without trained mental health professionals. Depressive symptoms were not measured by a “blind” rater, but the reports of clinicians and participants were similar. Only 4 clinical sites were selected for randomization; therefore, site-specific characteristics (participants and staff) may have contributed to the outcomes. COMB sites enrolled a smaller proportion of eligible participants, possibly introducing group differences. In fact, COMB and TAU groups differed by gender and transmission category, although these factors were not found to affect study outcomes. Previous research has found that gender does not predict acute response, although it may impact relapse.48,49 Although youth with perinatal transmission may differ from those with other modes in their extent of medical care and neuropathology, which could impact psychiatric treatment, the small number of perinatal youth (four) precludes examination of this important issue. COMB sites implemented structured treatment with supervision to assure treatment fidelity, but treatment at TAU sites was not monitored. Inherent differences in skill or impact of providers cannot be ruled out. Nonetheless, once enrolled, sites in both conditions did equally well in retaining youth for study assessments, so, by that measure, the relationship between the sites and participants appears comparable. Data on the mental utilization at sites were not obtained after the end of treatment, limiting our understanding of the reason for the sustained remission rate in COMB.
This preliminary trial found that combined CBT with MI skills and stepped-care MMA guided by symptom measures resulted in a significant reduction in depressive symptoms for YLWH. The combined intervention was delivered in the medical care setting by existing staff, suggesting that COMB, tailored for YLWH is feasible in other US medical care sites. The improvement in depression was maintained for an additional 24 weeks beyond the 24-week intervention period, suggesting that COMB could have a lasting impact. It is left to future research to confirm these findings in other sites, examining the moderating impact of factors such as gender, age, or route of transmission, and any sustained changes in treatment delivery by sites. The extension of efficacious interventions for depression to centers out of the United States, where the burden of HIV is greater, is also imperative.
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